Blood processing system

ABSTRACT

A blood processing system ( 2 ), includes a housing ( 4 ), to which a user control panel is mounted, having an access opening ( 47 ) therein. A cassette assembly ( 22 ), mounted to the housing for movement between a use position covering the access opening and a cassette-replacement position, includes a cassette holder and cassette ( 26 ) removably mounted to the holder. The cassette includes in part by tubing aligned with a through-hole ( 45 ) in the cassette. A door ( 34 ) is mounted to the housing for movement between a latched position, capturing the cassette between the panel and the door, and a released position. Independently-driven roller assemblies ( 46, 54, 72 ) pass part-way through the access opening to capture first tubing portions ( 44 A,  52 A,  68 A) between the roller tracks ( 100, 102, 104 ) and the roller assemblies for peristaltic pumping of fluid. A number of movable pinch elements ( 48, 80, 90, 96 ) are extendable through the front panel to selectively pinch the tubing against the door and thus seal the tubing.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional application of U.S. application Ser.No. 09/419,216 filed Oct. 15, 1999, which is incorporated by referenceherein.

BACKGROUND OF THE INVENTION

Blood processing systems are used for a range of purposes. They areused, for example, to collect blood from donors, for autotransfusionwhere blood lost by a patient during an operation is collected, cleanedand reintroduced into the patient's circulatory system, to preparecollected blood for freezing, to deglycerolize frozen thawed red cells,for washing red blood cells and for washing frozen thawed platelets.

There are features which would be very desirable with virtually allblood processing systems but are not provided by current systems. Tounderstand these desirable features one must first fully appreciate thepractical aspects of the blood processing technology as discussed below.The desirable features are small size of equipment, acceptably priceddisposables, automatic operation, protection from operator error,protection from equipment error, speed of operation and completeone-step processing.

Considering first a blood collection system, the collection of bloodfrom donors takes place both at blood banks and via use of mobile unitsduring so-called blood drives with the mobile unit collection oftenexceeding that at the blood banks. Accordingly, it is desirable to haverelatively compact systems so that a larger number can be easilytransported to the site of blood collection. Fast blood collection isdesirable since if donor comfort is increased by reducing the donationtime it is easier to attract donors.

Whole blood has usually been collected from a donor via gravity flow;alternatively, use of a blood removal roller pump has been used to aidcollection from a donor. The whole blood was then transported to a bloodprocessing facility and centrifuged to separate the plasma from theerythrocytes. In some instances a leukocyte filter was used on the wholeblood or on red cells to reduce the chance for undesirable patientreactions to donor leukocytes when donor red cells were later transfusedinto a patient. This whole blood collection procedure suffers from anumber of drawbacks. One major drawback is that the procedure is highlydependent on the skill of the operator taking the blood donation, thusrequiring extensive and expensive training of operators. Also, thecurrent procedures require nearly constant operator attention, therebylimiting the amount of blood which can be safely collected in a giventime period; i.e., the operator can only safely oversee a limited numberof blood donations at any one time. There is also a drawback that havingseveral people handle the whole blood as it is collected and separatedinto its component parts increases the chance of operator error. Anotherdrawback is that the several steps required, even if carried out by asingle operator, increase the risk of contamination of the whole bloodand of its separated component parts.

An apparatus has also been proposed which has the capability of fullyprocessing blood at the collection site but it is relatively bulky andrequires the use of a built in rotating centrifuge. The apparatus has anumber of limitations which include cost, relative bulkiness, thepossibility of leaks at rotating seals, relatively slow speed since allblood must be collected prior to the beginning of separation intocomponents, etc., and the requirement of close operator supervision. Theapparatus is disclosed in U.S. Pat. Nos. 5,651,766; 5,728,060; and5,733,253.

Another blood processing system, called an intraoperativeautotransfusion system, is commonly used during certain operations, suchas orthopedic surgery and open-heart surgery, when a great deal of bloodcan be lost by the patient. In autotransfusion the lost (shed) bloodalong with air, particulate matter and diluting solvents are collected.The air, solvents, and particulate matter are removed. The cells arewashed and the hematocrit is increased to a desired level such as thatnormally present in the body (about 40%). The resulting blood-cellsuspension is transfused back into the patient. Autotransfusion reducesthe cost and problems (incompatibility and infection) associated withblood bank blood. It would be desirable to have a relatively small sizeunit since operating rooms constitute a highly crowded environment.Furthermore, automatic operation is desirable as it allows medicalpersonnel to attend to other matters while the autotransfusion unitcarries out the desired task of collecting and cleansing red blood cellsfor re-infusion. Low cost of disposables is necessary since if the costis too high even the technically best available system may not be used.The system set forth in U.S. Pat. Nos. 5,242,384 and 5,423,738 isadapted for automated autotransfusion but the high cost of the complexdisposable and its tangential flow separator has prevented this systemfrom wide commercial acceptance.

Another type of blood processing system is the thawed blood processingsystem. It is intended to remove glycerol and free plasma hemoglobinfrom thawed frozen red blood cells. It is primarily used by the militaryon land and aboard ship to provide red cells in emergency situations.The military has stockpiled a large number of units of blood, all of oneuniversal donor type, for this purpose. Frozen blood is also commonlyused when a patient undergoing elective surgery desires to stockpile hisor her own blood for use during the surgery. Frozen blood is also usedto supply rare blood types.

One of the problems with using frozen blood is that it requires thatsome type of agent be added to the red blood cells to allow them to besafely frozen; glycerol has commonly been used for this purpose. Also,some red blood cells are damaged by the freezing process. Once thawed,these damaged red blood cells release free plasma hemoglobin. Both theglycerol and free plasma hemoglobin must be reduced to safe levels inthe thawed blood and saline and a red cell storage solution must beadded to the thawed blood before transfusion into a patient. Once again,small size, automatic operation and low cost are important factors.

Another blood processing system is used for washing red blood cells.Blood is collected, separated into its components and concentrated redblood cells are stored in a bag which contains the storage solution topreserve the red cells. Once again, small size, automatic operation andlow cost are important factors.

A further blood processing system is used to wash frozen thawedplatelets. In this system the platelets are frozen with, for example,DMSO, and possibly other preservatives. When the frozen platelets arethawed, the DMSO and possibly other preservatives are preferably washedfrom the platelets before the platelets can be used.

U.S. Pat. Nos. 5,670,312; 5,460,493; 5,311,908; 5,273,517; 5,195,960;4,985,153; and 4,385,630 disclose various types of blood processingsystems and system components.

SUMMARY OF THE INVENTION

One aspect of the present invention is directed to a blood processingsystem designed for the automatic or semi-automatic processing of bloodduring processing procedures such as blood collection from a donor,intraoperative autotransfusion, thawed red blood cells processing,washing fresh red blood cells, and washing thawed platelets. The systemprovides for the use of an easily removable and replaceable cassettewhich contains all of the disposable components.

The blood processing system includes a housing having a panel; usercontrols are preferably mounted to the panel. The system also includes acassette assembly mounted to the housing adjacent to an access openingin the panel for movement between a use position, adjacent to andcovering the access opening, and a cassette-replacement position. Thecassette assembly includes a cassette holder and cassette removablymounted to the holder. The cassette includes a cassette body having oneor more through-holes. The cassette also includes flow channels definedat least in part by tubing, the tubing having first and second portionsaligned with the through-holes. The cassette preferably carries all ofthe disposable elements, such as filter, separator, and tubing.

The system also includes a fastening assembly, typically a door, movablymounted to the housing for movement between a latched position,capturing the cassette between the panel and the door, and a releasedposition. In an embodiment of the invention the door has roller trackspositioned to engage the first tubing portion when the cassette assemblyis in the use position and when the door is in the latched position. Aroller pump drive assembly is mounted within the housing and includesindependently-driven roller assemblies. Each roller assembly includes anumber of circumferentially positioned rollers. Each roller assembly ispreferably mounted for rotation about a common axis. Each rollerassembly is located to be aligned with the access opening and alignedwith a corresponding first tubing portion. The first tubing portions inthis embodiment are captured between the roller tracks on the door andthe roller assemblies so that fluid is pumped through the first tubingportions by rotation of the roller assemblies.

A number of movable pinch elements are mounted within the housing andare aligned with the second tubing portions. The pinch elements aremovable to selectively pinch the second tubing portions against thedoor, thus closing the tubing, when the door is in the latched position.A controller is operably coupled to the operator controls, roller pumpdrive assembly, cassette assembly and pinch elements.

A blood processing system made according to an embodiment of theinvention is preferably designed so that the pumping rate and pumpedvolume are controlled by monitoring the pressure or other parameterswithin the system. When the system is used to pump blood from a donor,it is desired to pump the blood from the donor as fast as possiblewithout harming the donor, such as collapsing a blood vessel, ordamaging the blood being withdrawn. With the present invention thepumping rate of blood pumped from a donor can be determined andcontrolled by, for example, monitoring the drop in pressure along aportion of the flow path within the system and adjusting the pump speedto achieve a desired pressure level. By doing so, the pumping pressurecan be maintained in an optimal range for a donor so that the vessel isnot collapsed.

The system can be designed to automatically collect blood and shut downafter collecting a chosen volume.

The hollow fiber separator is used to separate fluid from a cellularsuspension (blood or blood components) flowing through it. A preferredhollow fiber separator includes a number of microporous hydrophilichollow fibers arranged in a bundle of parallel fibers. The porous wallsof these fibers have pore size that on average is about 0.2 to 0.5microns in diameter. The fiber bundle is placed in a housing thatclosely surrounds the outside of this bundle. The ends of this bundleare potted and sealed with a liquid material such as polyurethane thatsolidifies and fills the spaces between the housing and all of thefibers. Each end of the bundle is then cut through the potting materialat the ends of the housing. This exposes the lumens of the fibers. Endcaps are secured and sealed to each end of the housing. A port in eachend cap leads fluid into or out of the chamber formed by the inside ofthe end cap and the cut ends of the fibers. Fluid containing cells (redcells or platelets) flows in one end cap, through the lumens of thefibers, and out the other end cap. A port in the wall of the housing isused to remove fluid which passes through the pores of the fibers fromthe outside surfaces of the fibers. This removed fluid typically comesfrom the fluid flowing through the lumens of the fibers. The removedfluid consists of a liquid containing salts, free plasma hemoglobin,possibly anticoagulant, possibly glycerol, other dissolved matter, andsmall particulates. The removal process is called tangential orcross-flow separation. The high velocity of flow inside the fibers keepscells and other material away from the wall and prevents pore pluggingor layering that can decrease removed fluid flow rates. The pressurelevels at the end cap entrance and exit of the separator and at theremoved fluid port affect removed fluid flow rate. A pump can be used tocontrol this flow rate. Increases in the pressure differential acrossthe fiber wall can increase removed fluid flow rate up to the point thatsignificant and undesirable cellular layering occurs on the insidesurfaces of the fibers which reduces removed fluid flow rate. Thepressure differential and blood flow rate are controlled to preventthis.

When whole blood is concentrated by a hollow fiber separator andseparated into red cells and plasma, plasma is the removed fluid. Arecirculation process is preferably used to concentrate the red cells toa high hematocrit and to separate the plasma into a bag.

The washing of red cells or platelets preferably occurs by separatingthe removed fluid or waste from the cells with waste fluid flowingthrough the walls of the hollow fibers, out the plasma port, and into awaste bag. Saline or another solution is added at the cellular flow exitof the separator at a flow rate essentially equal to the waste flow. Thesaline is made to mix well with the cellular flow in a mixing tee andtubing. Then the cellular flow enters into the recirculation bag, goesinside the recirculation bag, goes out of the recirculation bag, andenters into the separator at a constant hematocrit, perhaps 45%. Therecirculation bag can be mixed by mechanical manipulation to ensure aconstant hematocrit is maintained in the bag and that the concentrationof removed matter (e.g. free plasma hemoglobin; anticoagulant; glycerol)is uniform within the recirculation bag to ensure consistentperformance. The wash process is then a continuous waste removal andsaline or wash fluid replacement process that rapidly decreases theconcentration of removed matter in the recirculation bag. Higherrecirculation bag hematocrits, higher cellular fluid flow rates, andhigher changes in hematocrit across the separator tend to improve theefficiency and speed of removal.

The most expensive component of the cassette is typically the plasmaseparator, such as a hollow fiber separator. One of the primary aspectsof the invention is the recognition that a less expensive separator canbe used if the system is designed so that blood can be selectivelyrecirculated to pass all or part of the blood through the separator morethan once until the desired separation, typically measured byhematocrit, has been achieved. Doing so reduces the cost of thedisposable cassette without reducing the effectiveness of the system.Recirculation can be achieved, for example, using appropriate pinchvalves and the main blood pump or with the aid of a separate bloodrecirculation pump. Recirculation may, or may not, involve the use of arecirculated blood reservoir.

A primary advantage of the invention is the interchangeability of thecomponents and the ease of modifying the invention to accommodatedifferent blood processing systems. For example, it is often possible tomodify the blood processing system to accomplish different tasks, forexample blood collection, autotransfusion, thawed blood processing, orred cell washing, by simply modifying the specific computer program usedto run the controller, and changing the number and types of bags, wherethe bags are hung and how the bags are hooked up to the remainder of thesystem. Only the disposable cassette will usually be speciallyconstructed for a particular procedure or process. Because the samegeneral system can be used for a wide variety of specific bloodprocessing tasks, economies of scale, and thus lower user cost, can beachieved.

Another advantage of, and a further aspect of, the invention is that thecassette can be easily tested to ensure that it is leak-free, which is avery necessary attribute for the system. This can be accomplished simplyby pressurizing the flow channels and determining the rate of anydrop-off in pressure. Any unacceptable cassettes can be either discardedor reworked prior to being shipped to solve the problem.

It is important that the system not be run when, for example, the sourceof blood or of a supplemental fluid, such as saline or anticoagulant, isnot connected to flow channels of the cassette, or when the source isempty, or when a valve is incorrectly closed, or when a line is crimped.Various detectors non-invasively provide the necessary signals to thecontroller so that the controller can shut down pumping by halting therotation of the roller assemblies and/or closing pinch valves should anyof these problems occur. Doing so helps reduce the negative results ofoperator error or product failure.

It is important that the cassette be positioned so that tubing is notimproperly engaged in the latched position. It is important to providestructure to accomplish this and, at the same time, properly align thetubing on the cassette relative to the roller assemblies and the pinchelements for proper operation. This is aided by ensuring that thecassette is properly positioned in the cassette holder so that with thecassette assembly in the use position and the door in the latchedposition, all elements are properly aligned. The proper positioning ofthe cassette in the cassette holder is aided by the fact that gravityhelps keep the cassette properly and fully engaged within and supportedby the cassette holder. Also, or as an alternative, appropriate guideelements, such as tapered pins, extending from the housing or thecassette can be used to engage appropriately located guide holes in thecassette or the housing when the cassette assembly is in the useposition.

Accurate but non-invasive pressure measurements taken along the flowchannels are important to, for example, ensure correct and safe pressurelevels and to control fluid flow rates by monitoring pressure dropsacross a pressure drop device such as a laminar flow tube. This can beachieved using sealed diaphragm pressure access ports along the flowchannel; the pressures at such ports are preferably coupled to apressure sensor which provides a pressure signal to the controller foreach pressure access port monitored. Fluidly coupling the pressuresensor and the pressure access ports is preferably automatically made asthe cassette is secured into its use position and the door is placedinto its latched position.

It is also important to add anticoagulant to the blood and mix the twowell. When blood is recirculated and stored in a recirculationreservoir, it is important in some uses to ensure that the blood isthoroughly mixed with inlet blood entering the reservoir along with asaline or other solution for effective red cell washing. This can beaccomplished by automatically and mechanically manipulating the bag-typereservoir by, for example, flexing, kneading or punching the bag-typereservoir. Such mechanical manipulation of a bag-type reservoir simplyand thoroughly mixes the contents of the bag but without any physicalcontact with the blood. Thorough mixing can, for example, also beaccomplished by pumping from one reservoir into another reservoir orthrough the use of mechanical stirrers.

Mechanical bag manipulators preferably act on vertically-hung bags sothat the contents of the bags can be mixed while processing without theneed for special supports or alignments of the bags. Whilevertically-hung bags can have their contents mixed by shaking the entirebag support, this is not usually preferred because of problems caused bythe shaking, such as loosening of fittings, noise, etc.

Other features and advantages will appear from the following descriptionin which the preferred embodiments have been set forth in detail inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified overall view of an automatic blood collectionsystem made according to an embodiment of the invention showing acassette assembly in the use position and the door in the latchedposition;

FIG. 2 is a simplified exploded isometric view of the panel, cassetteassembly and door of the system of FIG. 1;

FIG. 2A is a schematic illustration of the automatic whole bloodcollection system of FIG. 1;

FIG. 3 is a side elevational view of the front panel portion of thesystem of FIG. 1 showing the door in a released position and thecassette assembly in a cassette replacement position;

FIG. 4 is a view of the infacing side of the door of FIG. 3, that is theside facing the cassette assembly;

FIG. 5 illustrates the outfacing side of the cassette assembly of FIG.3;

FIG. 6 is an end view of the cassette assembly of FIG. 5;

FIG. 7 is a view of the inner surface of the cassette of FIG. 3;

FIG. 8 is a plan view of the panel of FIG. 3 with the door and cassetteassembly removed;

FIG. 9 is a partially exploded view of the center roller assembly ofFIG. 8 illustrating the pivotal mounting of a roller;

FIG. 10 shows the rollers of the center roller assembly of FIG. 8engaging a tubing segment, the tubing segment captured between therollers and an arcuate roller track of FIGS. 3 and 4, and showing theoffset placement of two of the three drive motors for the three rollerassemblies;

FIG. 11 illustrates the roller pump drive assembly including the threeroller assemblies and three drive motors with the offset, overlappingorientation of the drive motors shown;

FIG. 11A is a simplified side cross-sectional view illustrating coaxial,nested drive shafts used to drive the roller assemblies;

FIG. 12 is a schematic illustration of an autotransfusion system madeaccording to the invention;

FIG. 13 is a schematic illustration of a thawed blood processing systemmade according to the invention;

FIG. 14 illustrates an alternative embodiment of the thawed bloodprocessing system of FIG. 13;

FIG. 15 illustrates a blood glycerolization processing system madeaccording to the invention;

FIG. 16 illustrates an alternative embodiment of the automatic bloodcollection system of FIG. 2A;

FIG. 17 illustrates an alternative embodiment of the automatic bloodcollection system of FIG. 16 which permits two units of blood to becollected from a single donor;

FIG. 18 is an overall view of an alternative embodiment of the system ofFIG. 1;

FIG. 19 is a view of the system of FIG. 18 with the front door open, thecassette removed from between the front door and the front panel and thevarious bags coupled to the cassette removed from the bag hanger; and

FIG. 20 is a view of a portion of the front door of FIG. 19 similar tothe view of FIG. 4 illustrating a bag shaker support surface positionedopposite a reciprocating bag shaker shown in FIG. 19.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

FIG. 1 illustrates an automatic blood collection system 2 made accordingto an embodiment of the invention. System 2 is a substantially fullyautomated system which swiftly, and with minimal operator handling andattention, automatically removes blood from a donor and separates thewhole blood as taken into its component parts. System 2 includes ahousing 4 having a top 6 supporting a bag hanger assembly 8. Bag hangerassembly 8 includes a mechanical bag manipulator 10 which is designed sothat it can mechanically manipulate a storage bag 12, housed withinmanipulator 10 so as to help mix the contents of bag 12.

System 2 also includes a front panel 14 to which a user control panel 16is mounted. User control panel 16 typically includes a number of inputpads or buttons 18 and a display 20. While control panel 16 ispreferably mounted to housing 4, it can alternatively be physicallyseparated from the housing and operably coupled to the housing by, forexample, cables.

Referring now also to FIG. 2, system 2 is seen to include a cassetteassembly 22, including a generally U-shaped cassette holder 24 and aremovable, and typically disposable, cassette 26. Cassette holder 24includes a pair of side rails 28 defining inwardly facing grooves withinwhich the lateral edges 30 of cassette 26 slide. Cassette holder 24 ispivotally mounted to a support rod 32 mounted to and parallel with frontpanel 14. The orientation and configuration of cassette holder 24 andcassette 26 causes cassette 26 to be maintained fully housed withincassette holder 24 by gravity and by the friction between the lateraledges 30 of cassette and side rails 28 of holder 24.

System 2 further includes a door 34 having a mounting block 36 at thelower end. Door 34 is also pivotally mounted to front panel 14 throughthe use of support rod 32 passing through mounting block 36. Therefore,cassette assembly 22 and door 34 both pivot about a common axis definedby support rod 32.

Cassette assembly 22 can be pivoted between a use position, adjacent tofront panel 4, as shown in FIG. 1, and a cassette replacement position,at which cassette assembly 22 is pivoted away from front panel 14, asillustrated in FIG. 3. Door 34 can be pivoted between a latchedposition, shown in FIG. 1, at which door 34 is latched to housing 4 thuscapturing cassette 26 between door 34 and panel 14, and a releasedposition, shown in FIG. 3, at which the door is pivoted away from panel14 thus permitting the free access to cassette 26. Door 34 covers aportion of cassette 26 when in the latched position of FIG. 1.

Cassette 26 is designed for blood collection from a donor. Cassette 26includes a body 38 which can be used for additional blood processingprocedures as will be discussed in more detail below with reference toFIGS. 12 and 13.

Blood processing system 2 will now be discussed with reference to aschematic representation of the system shown in FIG. 2A. System 2 usesthree pumps 46A, 54A and 72A; each pump is made of a respective rollerassembly 46, 54 and 72 which engages a respective tubing segment 44A,52A, 68A (see also FIG. 5), the tubing segment being captured betweenthe roller assembly and an associated roller track 100, 102, 104 (seeFIGS. 3 and 4) on door 34 when the door is in the latched position ofFIG. 1. With system 2, blood is pumped from the donor through a needle40, inserted into an appropriate donor blood vessel, and through a line42. Line 42 continues to cassette 26, the intersection of line 42 andthe cassette indicated by a dashed line in FIG. 2A. Note that the linesor tubes coupling cassette 26 with needle 40 and the various bags shownin FIG. 1 are shown in FIG. 2A only for the sake of clarity ofillustration in the other figures.

Line 42 continues within cassette 26 as line 44. A segment 44A of line44, aligned with a through-hole 45 in cassette 26, is engaged by a bloodpump roller assembly 46, which passes through an access opening 47 inpanel 14, after line 44 passes a pinch valve plunger 48 (see FIGS. 2 and8) at a plunger opening 48A (see FIGS. 5 and 7) in cassette body 38.System 2 includes four pinch valves 48A, 80A, 90A and 96A; each pinchvalve is made up of a respective pinch valve plunger 48, 80, 90 and 96which engages a tubing segment 44A, 76A, 68C and 94A (see FIGS. 5 and7), the tubing segments being selectively pinched closed between thepinch valve plungers and an associated raised element 110 (see FIGS. 3and 4) on door 34 when the door is in the latched position of FIG. 1.

Anticoagulant from an anticoagulant bag 50 passes along a line 52 withincassette 26. Anticoagulant is pumped at a metered rate corresponding tothe rate of blood from the donor by an anticoagulant pump rollerassembly 54 which engages a line segment 52A and delivers theanticoagulant to line 42 at a T coupling 56 external of cassette 26.Since the blood being processed is anticoagulated before it is pumped bypump 46 a and thereafter processed, blockage problems are minimized.

Cassette body 38 (FIG. 6) has a number of U-shaped channels 57 sized toreceive the various lines 44, 52, 68, 76 and 94. The lines aremaintained in position across openings 45, 48A, 80A, 90A and 96A and canbe affixed within channels 57 using an adhesive. Therefore when rollerassemblies 46, 54, and 72 engage their associated tubing segments 44A,52A, 68A, the locations of tubing segments are accurately fixed toprovide consistent flow rates. Affixing the tubing in channels 57 helpsto ensure the correct tubing segment is engaged by the correct rollerassembly and pinch valve plunger. The arrangement of the plungers (suchas plungers 48, 80, 90, 96) and their associated solenoids, see FIGS. 2and 8, in a staggered, two-dimensional array allows for the apparatus tobe more compact and the disposable cassette 26 to be smaller and thuscost less.

The operations of the various components are controlled by a controller58 housed within housing 4 and coupled to control panel 16 and apressure sensor 60 as indicated by signal terminals P1, P2 and SP1–SP8.Controller 58 is a conventional microprocessor-based control systemdeveloped for blood processing systems and similar products. Controller58 thus controls the actuation of blood pump roller assembly 46,anticoagulant pump roller assembly 54 and pinch valve plunger 48according to the particular programming of controller 58 and pressureinputs from diaphragm-type pressure access ports 62, 64. Thesediaphragm-type pressure access ports permit accurate access to pressureswithin cassette 26, but do so without compromising the sterility of thesystem. The pressure measurements are made by using a pressure isolationdevice (not shown) at each pressure access port 62, 64. Each pressureisolation device includes a flexible diaphragm sealed on each side to arigid enclosure or housing. The fluid to be measured flows on one sideof the diaphragm. The other side of the diaphragm is exposed to atrapped air volume that communicates with a pressure transducer inpressure sensor 60 through access ports 62, 64 and associate pneumaticlines (not shown). The flexibility of the diaphragm ensures that the airpressure measured by the transducer equals the fluid pressure on theother side of the diaphragm.

An alternative approach is to allow the air side of the diaphragm of thepressure isolator to directly contact the flat face of a pressuretransducer. The pressure sensor will then directly measure the fluidpressure on the other side of the diaphragm. Other pressure sensordevices may also be used.

Line 44 continues to a T coupling 66 at which line 44 splits into arecirculation loop 68. Recirculation loop 68 has a number of componentsalong the loop. First along loop 68 is an optional whole blood filter 70which, for example, uses a screen or pad or mat of fibrous material totrap leukocytes (white blood cells) and platelets by adhesion. Anexample of whole blood filter 70 is one made by Pall Corporation of EastHills, N.J., and as described in U.S. Pat. No. 4,985,153. Recirculationloop 68 also has a recirculation pump 72A along its length. A plasmaseparator 74, often referred to as a tangential flow separator, alongloop 68 is used to remove plasma from the blood passing along loop 68,and directs the plasma through a plasma line 76 to a plasma bag 78.Plasma separator 74 is preferably a hollow fiber type of separator madefor this application. A pinch valve 80A selectively seals off line 76 asdiscussed below. The recirculation of the blood through therecirculation loop 68 allows use of a plasma separator 74 which hassignificantly less fiber surface area than would be necessary if theblood was passed through it only a single time. Generally the fibersurface area of the separator can be reduced to only about one-third ofwhat it would have to be in the absence of the recirculation loop 68.While providing the recirculating loop 68, recirculation or storage bag12 (usually), and pump 72A requires a slightly higher capital cost thanwould be required in the absence of these components, the saving in costof disposable plasma separators soon dwarfs this added capital expense.The way that the apparatus works is that the hematocrit (generally equalto the fraction of red blood cells) is increased significantly with thefirst pass through the plasma separator 74 and then increased again witheach successive pass until the desired increase in hematocrit isobtained.

A thermoelectric cooler 82 extends from front panel 14, passes through aslot 83 in cassette body 36 and engages a segment 68B of loop 68 toselectively cool blood passing along loop 68. Thermoelectric cooler 82includes a thermoelectric element and an attached heat sink thatcontacts tubing segment 68B for heat removal. A temperature measurementdevice (not shown) is used to measure and maintain, via feedback to atemperature controller, the desired tubing or heat sink temperature.

Recirculation loop 68 continues out beyond cassette 26 and connects to arecirculation storage bag 12 at a bag entrance 84 and at a bag exit 86.A pinch valve 90A selectively seals loop 68 between bag exit 86 and Tcoupling 66.

Recirculation pump 72A operates at a much higher pumping rate than bloodpump 46A. As the blood recirculates along loop 68, plasma is removed byplasma separator 74 to increase the hematocrit of the recirculatingblood. During these operations, pinch valves 80A and 90A are both open.

During normal blood collection procedures, blood pump 46A operates untila fixed volume, such as 450 ml, of blood has been withdrawn from thedonor. It is important to ensure that blood pump 46A does not operate sofast as to cause the donor's veins to collapse or create otheruncomfortable or dangerous situations. This can be achieved in part bycontrolling the rate of blood pump 46A and by monitoring the pressure atpressure access port 62.

An understanding of the flows involved may aid in an understanding ofthe technology involved and of the invention. As mentioned, the wholeblood processing technique of the invention suitably uses recirculationthrough a hollow fiber plasma separator 74 so that a relatively lowsurface area hollow fiber plasma separator 74 can be used therebykeeping costs of disposables down. FIG. 2A illustrates one embodiment ofthe invention which utilizes the recirculation technique. Blood rollerpump 46 can be used to extract blood from a donor at the maximum ratewhich will not collapse the donor's vein (venous pressure is normallyabout 0 to 20 mmHg). This serves to reduce the time the donor must behooked up to the blood collection apparatus. If a sudden drop inpressure occurs, this indicates the pump rate is too high and thecontroller reduces it. The pressure drop through needle 40 andassociated tubing 42 to pressure access port 62, just upstream of bloodroller pump 46 is known/calculable (ΔP=Q1×R where Q1 is the blood flowrate and R is the resistance of needle 40 and tubing 42 upstream ofpressure access port 62—somewhat of a function of the donor'shematocrit—the venous pressure, Pvenous is then equal to P1 (thepressure measured by pressure access port 62)+Q1×R). The feedbackcontrol scheme maintains the calculated Pvenous at about 0 to 20 mmHg byvarying Q1. There is typically about a 10–50 mm drop through theoptional whole blood filter 70 which is downstream of blood roller pump46. A pressure access port 64 is located downstream of pressure accessport 64 and has a pressure drop across it of typically 200–400 mm. Theenriched red blood cell output from the hollow fiber plasma separator 74is partially pumped by recirculation pump 72 between filter 70 andpressure access port 64 and then again through hollow fiber plasmaseparator 74. Recirculation is continued until the blood hematocrit israised from the donor value, normally about 40%, to the desired value,normally about 80%. The flow through the recirculation pump is adjustedsuch that P2=K, where K is an empirically determined constant between150 and 300 mmHg selected to maximize plasma flow without causingexcessive hemolysis. P2 is the pressure measured by pressure measurer 64and Q2 is the flow rate through the recirculation loop. The relationshipamong Q2, P2 and H2 is as follows: ${Q2} = \frac{P2}{C({H2})}$

where H2 is the mixed blood hematocrit entering the separator and C is aconstant dependent upon separator design parameters and temperature.Then when H2 reaches 80%, a value of Q2 is reached that correlates withthis hematocrit. When this occurs the recirculation process is stoppedby the controller 58. The overall flow equation is Q1=Q2+Q3. Where Q1 isthe output flow from the blood pump 46, Q2 is the flow out of therecirculating bag 12 and into separator 74, and Q3 is the flow of plasmaout of separator 74 to the plasma collection bag 78. Flow rates Q1 andQ2 are controlled as described above via controller 58 which receivesthe various flow rate (pump speed) and pressure signals. Flow rate Q3 isnot controlled directly and is dependent upon P2, separator designparameters and blood parameters.

A somewhat different parameter, RS, may be used as a control parameter,instead of P2, to control and optimize the recirculation process, thatis to maximize waste flow and minimize hemolysis. RS is calculated asfollows: ${RS} = {{C({H2})} = \frac{P2}{Q2}}$RS is therefore a calculated parameter that is proportional to H2 and isderived from the measurement of P2 and Q2. R2 is in effect theresistance to flow of hollow fiber separator 74.

When the desired volume of blood has been withdrawn from the donor,blood pump 46A and anticoagulant pump 54A stop operating. Recirculationpump 72A continues to operate until the desired hematocrit reaches, forexample, 80%. The hematocrit is determined by measuring the resistanceto flow within plasma separator 74. This resistance to flow isessentially the pressure sensed at pressure access port 64 divided bythe flow rate through recirculation pump 72A. When the particularresistance value, corresponding to the desired hematocrit is reached,recirculation pump 72A stops pumping. Pinch valves 48A and 80A are thenactuated to seal off lines 44 and 76. A red blood cell storage solution,such as Nutricel, obtainable from Pall Corporation, contained within ared blood cell bag 92 is then fluidly coupled to line 44 at a T coupling98 by a line 94 by releasing pinch valve 96A. Blood pump 46A then isoperated to pump the red blood cell storage solution from bag 92 throughwhole blood filter 70, plasma separator 74, and into recirculation bag12. This not only flushes blood from that portion of loop 68, but alsoprovides the blood within bag 12 with the necessary storage solution.Bag 12, containing the concentrated red blood cells and storagesolution, and plasma bag 78, containing plasma, are then sealed off andremoved from bag hanger assembly 8 for storage, use, or furtherprocessing. Cassette 26, bag 92 and 15, needle 40 and associated tubingand lines (shown only in FIG. 2A) are typically disposed of.

Tubing segments 44A, 52A, 68A are, as mentioned above, captured betweenroller assemblies 46, 54, 72 and arcuate roller tracks 100, 102, 104,respectively, formed in a block 106 of door 34 as shown in FIGS. 3 and4. Door 34 also includes a block 108 having three rows of laterallyextending raised elements 110, positioned opposite the eight pinch valveplungers shown in FIGS. 2, 4 and 8. In the present embodiment, only fourof the eight pinch valve plungers, that is plungers 48, 80, 90 and 96,are used. The provision of additional pinch valve plungers and theirassociated plunger openings formed in body 38 of cassette 26 permits theinvention to be used to conduct other types of blood processingprocedures, two of which will be discussed below with reference to FIGS.12 and 13. Similarly, additional pump roller assemblies, in addition toassemblies 46, 54, and 72, could be provided to accommodate additionalpumps if needed. Note that the roller tracks 100, 102, 104 and theraised elements 110 can alternatively be provided on the cassette 26 inwhich case the through hole 45 is replaced by an indentation in thecassette 26.

Cassette 26 also includes up to four pressure couplers 112, one of whichis shown in FIG. 3. Each pressure coupler 112 includes a pneumaticfitting 114 (see FIGS. 2 and 8) which engages a complementary pneumaticfitting 116 on front panel 14 of housing 4 when cassette assembly 26 isin the use position of FIG. 1. Pneumatic coupling 112 also includes atube fitting 118. A flexible tube, not shown in any of the figures,extends from each tube fitting 118 to diaphragm-type pressure accessports 62, 64 (see FIGS. 2A and 5). This permits pressure in lines 44, 68to be sensed and monitored by pressure sensor 60 in a non-invasivemanner. Again, cassette 26 provides four pressure couplings, two morepressure couplings 112 than are needed for the embodiment of automaticblood collecting system 2. Doing so permits the same basic body 38 ofcassette 26 to be used for a number of different blood processingsystems. Providing extra pinch valve plungers and pneumatic fitting onfront panel 14 permits the same basic housing 4, door 34 and cassetteholder 24 to be used for a number of different blood processing systemsas well.

FIG. 9 illustrates a partially exploded view of roller assembly 54.Roller assembly 46 includes a rotatable frame 120 having eight mountingarms 122. Each mounting arm 122 mounts a roller 124 to its outer endusing a roller mount 126 pivotally mounted to the distal end of mountingarm 122. A set screw 128 secures a mounting pin 130 within coaxial bores132, 134 formed in arm 122 and roller mount 126, respectively. Roller126 is biased outwardly through the use of a compression spring 136captured between frame 120 and roller mount 126. The inner end of spring136 is maintained in place by being mounted over an annular spring guide138, the spring guide being held in place by a screw 139. Instead ofspring-biasing each roller 124 with a separate spring 136, each rollertrack 104 could be separately spring-biased against roller assemblies46, 54, 72. Also, each roller assembly 46, 54, 72 could be separatelybiased against door 34. Of course a combination of biasing schemes couldbe used.

Turning now to FIGS. 10, 11 and 11A, it is seen how all three rollerassemblies 46, 54, and 72 have been made to be individually driven, butpositioned at a very close axial spacing. FIG. 11A illustrates, in asomewhat schematic form, a main support shaft 140 which passes throughand radially supports each of the roller assemblies. Roller assembly 54is keyed to shaft 140 and thus is both supported by and is rotated byshaft 140. Roller assemblies 46 and 72 freely rotate on shaft 140 byvirtue of the use of bearings 142. Roller assemblies 46, 72 are securedto and driven by hollow drive shafts 144, 146 which are coaxial with andsurround main drive shaft 140. FIGS. 10 and 11 illustrate thepositioning of separate drive motors 148, 150, 152 which individuallydrive roller assemblies 46, 54, 72 through associated drive belts 154and drive pulleys 156. Since all drive connections are axially locatedthere are no gears or pulleys between the roller assemblies. Utilizingthis type of mounting structure with the motors as close together aspossible leads to an overall unit which is quite compact and minimizescassette size.

Automatic blood collection system 2 is typically used to automaticallycollect a predetermined volume of blood from a donor, remove leukocytesand platelets from the collected blood and also remove a certain amountof plasma from the rest of the blood until a desired hematocrit isachieved. By using a recirculation loop and separator flow control inthe loop to obtain the desired hematocrit, a much lower fiber surfacearea, and thus much less expensive, normally disposable, plasmaseparator can be used. This not only reduces the cost of collection ofeach unit of blood, it also reduces the size and bulk of the disposablecassette.

One aspect of the invention is the ability to test cassette 26 for leaksin a simple manner. Cassette 26 is preferably separate from cassetteholder 24 during testing, typically by the manufacturer. At this pointall tubes are open (not sealed by roller assemblies or pinch valveplungers). Each tube, except one, extending from the cassette is sealed.The one unsealed tube is coupled to a pressurized fluid source, such ascompressed nitrogen, to pressurize the tubing and components of thecassette. While continuing to monitor the pressure in the cassettetubing, the tubing is removed from the pressurized fluid source. Thepressure within the cassette tubing is then monitored to determine ifthere is an unacceptable drop in pressure over a chosen period of time.If the pressure drop is in excess of what is considered acceptable, thecassette is considered defective and removed for reworking, salvage ordisposal. It is important for cassette 26 to be leak-free during use toensure against contamination of the blood and to protect workers againstexposure to harmful, and sometimes potentially deadly, blood products.

Prior to use, door 34 is released from front panel 14 through the use ofa handle 160 carried by the door. This permits door 34 to be pivotedoutwardly away from front panel 14 from the latched position of FIG. 1to the released position of FIG. 3. Doing so also permits cassetteholder 24 to pivot from its use position, parallel to panel 14, of FIG.1 to its cassette replacement position of FIG. 3. This is preferablyaided by the use of a spring (not shown) captured between the base ofcassette holder 24 and front panel 14 to normally bias cassette assembly22 to its cassette replacement position of FIG. 3.

As an alternative, cassette 26 can have alignment holes (or pins) whichmate with pins (or holes) of the front panel 14. In this embodiment itis properly positioned by the hole/pin mating. Any desired structuralmethod, a door, snap fasteners, bolts, etc., can be used to fasten thecassette 26 in the latched position.

Cassette 26 and bags 12, 50, 78, and 92 come preconnected by tubing. Thetubing connecting the various bags and cassette 26 is not shown in thefigures, except for schematic FIG. 2A, for clarity. Bags 12, 50, 78, and92 are hung on bag hanger assembly 8 and cassette 26 is inserted betweenside rails 28 of cassette holder 24 until fully housed within cassetteholder 24 as shown in FIGS. 3 and 5.

Mechanical bag manipulator 10 is used to manipulate recirculation bag 12during the operation of system 2.

Once the various components are in place, controller 58 is set usinginput pads/buttons 18. For example, one of the pads/buttons can be usedto scroll through a number of different blood processing proceduresstored in the controller. When the automatic blood collection systemprocedure is displayed, that can be selected. The volume of blood to becollected can be preset or it can be changed by the user. A bar code onthe cassette can be used to identify the correct blood processingprocedure for that cassette. A bar code reader (not shown) on the systemimplements that procedure. Once the various input data are entered, thetubing is primed with fluid (normally anticoagulant solution), needle 40is inserted into a vein of the donor and system 2 is actuated.Initially, pinch valve plunger 96 is extended to seal line 94 while theremaining pinch valve plungers are retracted. Blood pump 46A beginsoperating to pump blood from the donor and into recirculation loop 68.Recirculation pump 72A, which runs at a higher pump rate than blood pump46A, forces the blood through recirculation loop 68 whereby leukocytesand platelets are removed, if desired, by whole blood filter 70 (filter70 is optional) and plasma is removed by plasma separator 74. Processedblood is then delivered to recirculation bag 12. Because pump 72A ispumping faster than pump 46A, blood from pump 46A and blood fromrecirculation bag 86 is pumped through recirculation loop 68. Thispermits the blood collected in bag 12 to have its hematocrit raised.During the operation of blood pump 46A, anticoagulant pump 54A alsooperates to direct a flow of anticoagulant from anticoagulant bag 50,the flow rate of the anticoagulant being proportional to the flow rateof the blood being drawn from the donor.

When it is determined that blood is no longer to be drawn from thedonor, which can occur automatically when a predetermined volume ofblood has been pumped or, for example, when a certain time period haselapsed, or upon manual intervention, blood pump 46A and anticoagulantpump 54A are halted and pinch valve plunger 48 is extended to seal line44 upstream of port 62. If necessary to achieve the proper hematocrit,recirculation pump 72A can continue to recirculate blood throughrecirculation loop 68. Once the desired hematocrit has been achieved,which is determined by sensing the resistance to flow through plasmaseparator 74, pump 72A is halted, pinch valve plunger 80 is extended andpinch valve plunger 96 is retracted. At this point, blood pump 46A isagain actuated to pump storage solution from bag 92 or anticoagulantfrom bag 50 through the initial portion of loop 68 and intorecirculation bag 12 thus flushing this portion of loop 68 as well asproviding bag 12 with the blood storage solution. Once the storagesolution has been pumped into the recirculation bag, pump 46A is stoppedand pump 46A is reversed causing the concentrated red blood cells andstorage solution in recirculation bag 12 to be pumped from bag 12, alongloop 68, through line 94 and into bag 92. Pump 46A is then stopped. Atthis point, bag 92 and bag 78 can be removed from system 2, typically byfirst clamping off and sealing the tubes extending to the bags and thensevering the tubes between the seals. Handle 60 is then manipulated toopen door 34. This permits cassette 26 to be removed from cassetteholder 24 so cassette 26, needle 40, anticoagulant bag 50, recirculationbag 12 and associated tubing can be disposed of.

FIG. 12 illustrates, in schematic form, an alternative embodiment of theinvention of FIG. 2A with like features referred to with like referencenumerals. Autotransfusion system 2A provides certain advantages,including completely automatic operation with simple setup. There isnegligible red blood cell loss, low hemolysis and low loss of plateletsto waste bag 194. System 2 is designed to reduce the blood volume alongthe various lines and within the various blood processing components tofacilitate purging. As with the embodiment of FIG. 2A, there are noblood attachments to make or break, and the system is a completelyclosed system. By eliminating the use of centrifugal bowl separationdevices, potentially leaky centrifugal bowl seals are eliminated. Also,as with the embodiment of FIG. 2A, system 2A is fail safe in thatfailure modes, such as a full or empty bag, can be quickly detected andautomatically responded to by virtue of the various pressuremeasurements and ultrasonic sensor air bubble detection.

Blood, along with entrapped air, diluent liquid, damaged cells, cellulardebris, and particulate debris, is suctioned from the surgical woundsite by a suction wand 162. Conventional methods of anticoagulation, notshown, are used. For example, a manually controlled heparin or CPD dripcan be provided at suction wand 162. The red blood cell containingliquid flowing from suction wand 162 passes into a blood reservoir 164,which hangs from bag hanger assembly 8. Blood reservoir 164 is suppliedwith a vacuum at vacuum port 166 to create the necessary suction atsuction wand 162.

Blood reservoir 164 may be a conventional cardiotomy reservoir having abuilt-in blood filter to remove particulate debris. Blood reservoir 164may contain a quantity of blood at the time it is coupled to thecassette. The commitment of the disposable cassette is usually not madeuntil the user believes there will be enough blood of sufficiently goodquality to justify conducting the processing procedure. Theblood-containing liquid accumulates in blood reservoir 164 until asufficient amount of blood is obtained to justify processing. Theblood-containing liquid from the blood reservoir 164 then passes intothe cassette, past an air bubble detector 168, along a blood entranceline 170. A blood filter 172 is located along line 170 and is used toremove particulate debris and some of the entrapped air. Blood filter172 will not be needed when blood reservoir 164 is a conventionalcardiotomy bag with its built-in blood filter. A blood pump 174,positioned further down line 170, initially operates at a fairly lowflow rate, such as about 200 ml/min. to 500 ml/min., and turns off ifair bubble detector 168 detects air bubbles, indicating a low or emptyblood reservoir. The blood-containing liquid is pumped through a laminarflow tube 176 positioned along line 170. Laminar flow tube 176 is usedto measure the hematocrit of the blood-containing liquid by the use of apair of pressure access ports 178, 180 on either side laminar flow tube176. Hematocrit can also be measured by, for example, the use of acalibrated optical detector for the direct measurement of hematocrit orthrough the use of pressure differential measurement across a hollowfiber separator 182 or by use of the inlet pressure to the hollow fiberseparator.

The blood containing liquid collected from a wound site often containssubstances which should not be reinfused back into the patient and itshematocrit is generally quite low due to dilution, typically from about5% to about 40% and subject to great variation. For example, suchsubstances as particulates (e.g., tissue fragments and thrombus),commonly removed by blood filter 172, and wash liquid, other bodilyfluids and cellular debris which is smaller than the pore size of thefiber surface (leached blood cells) are removed by a hollow fiberseparator 182 along line 170. Hollow fiber separator 182 has an inlet184 and an outlet 186 along line 170 and waste outlet 188 coupled to awaste line 190. Waste line 190 has a waste pump 192 which pumps liquid,such as non-blood fluids along with plasma and particulate waste whichpasses through the fiber pores, along waste line 190 to a waste bag 194,bag 194 also being supported by bag hanger 8. A pinch valve 198 alongthat portion of line 170 which couples exit 186 with a blood bag 196,and a pinch valve 230, located along a recirculation line 200 near a Tcoupling 204 along line 170, are closed during this initial pumping.Blood flows from separator 182 through recirculation line 200 and toblood recirculation bag 210. Line 200 extends from a T coupling 202 nearoutlet 186 to T coupling 204 between blood filter 172 and blood pump174.

Pinch valve 226, along line 170 between blood filter 172 and T coupling204, and pinch valve 228, along line 200 between T couplings 202 and206, remain open during this initial operation of the system. Blood ispumped along line 200 and into a blood recirculation bag 210, having anentrance 208 and an exit 222, until a desired volume, such as 200 ml, iscollected in bag 210 or until air bubble detector 168 indicates bloodreservoir 164 is empty. This ends the blood collection step.

To begin the blood concentration step, pinch valve 230 is opened andpinch valve 226 is closed. Blood is recirculated through loop 200 andhollow fiber separator 182 to raise the hematocrit up to any desiredvalue such as, for example, 45%. The control of the concentration stepis the same as that used for whole blood collection. One reason system2A is operated with a concentration step followed by a wash step isbecause the hematocrit of the blood in reservoir 164 can have ahematocrit of, for example, 5% to 40%. The wash process is much moreeffective if done at a higher hematocrit, for example, 45% or more: lesssaline is used and washing takes less time.

Saline pump 220, along saline line 214, is used to supply saline orother wash fluid to recirculation line 200 at a T coupling 206 between Tcoupling 202 and the inlet 208 of blood recirculation bag 210 during theblood washing step. A saline bag 212, supported bag hanger 8, containsthe supply of saline. Saline line 214 includes an air bubble detector218 which is monitored so that operation pump 220 can be halted when thesupply of saline wash fluid is low or exhausted.

Blood recirculation bag 210 is housed within mechanical bag manipulator10 to permit the contents of bag 210, that is the cleaned blood andsaline wash fluid, to be thoroughly mixed within the bag. Bagmanipulator 10 is designed to knead, punch, shake or otherwisemanipulate bag 210. Blood recirculation bag 210 has an outlet 222through which the blood and saline wash fluid pass through the remainderof segment 200. An air bubble detector 224 is used along line 200 toindicate when bag 210 is empty. Both saline pump 22 and blood pump 174operate while the blood is being washed. Saline is added at about thesame rate as waste fluid is removed from separator 182 by pump 192. Bagmanipulator 10 operates during both the concentration mode, during whichthe hematocrit is raised to about 45%, and during the washing mode,during which saline or other wash solutions are pumped by saline pump226.

At the end of the wash step, the hematocrit of the blood is preferablyabout 55%. Pinch valve 228 is then closed, pinch valve 198 is opened andsaline pump 220 is turned off so that the washed blood is pumped by pump174 from bag 210 into bag 196.

After the blood has been pumped into blood bag 196, pinch valves 198 and230 are closed, pinch valves 226 and 278 are opened, blood pump 174 isoperated and air bubble detector 168 is monitored to determine if bloodreservoir 164 has blood in it. If it does, the process is repeated.

When air bubble detector 168 detects air bubbles, blood pump 174 stopsand reverses direction and saline pump 220 is operated to pump the bloodin the lines and saline back through the lines into blood reservoir 164.This is done to eliminate air in the lines and components because aircan interfere with proper operation of some components, such asseparator 182, and can cause hemolysis. Unless the operator either turnssystem 2A off or places system 2A in a pause mode, controller 58 startspump 174 after a waiting period, for example 15 or 20 seconds, todetermine if blood reservoir 164 has blood in it.

System 2A is typically operated in three different modes. During thestandard mode about 90–92% of the free plasma hemoglobin, anticoagulantand other waste material are removed by operating the wash cycle (duringwhich saline pump 220 is pumping a wash solution into the recirculatingblood) for a predetermined period of time, such as about 2 to 5 minutes.The second mode is called the orthopedic mode; the wash cycle isoperated for a longer period of time and a greater, specific consumptionof saline solution to get about a 98% removal of the waste material.This higher waste material removal is needed in order to wash out thehigher initial levels of free plasma hemoglobin and small particulatedebris. The third mode is called the fast mode. During the fast mode thewashing step is eliminated so that saline pump 220 is not operated; theblood is passed through separator 182 to raise the hematocrit to about40% and remove some amount of waste material. Once the desiredhematocrit level is reached, the concentrated blood is pumped into bloodbag 196. The fast mode is suitable for surgical procedures that resultin loss of relatively clean blood.

Thawed blood processing system 2B is illustrated in schematic form inFIG. 13. System 2B is intended to remove glycerol and free plasmahemoglobin from thawed, previously frozen blood. The use of theinvention enables the storage of deglycerized red cells on the order ofa few to several weeks because the system uses a closed and steriledisposable cassette. This is a major advantage over other thawed bloodprocessing systems which use centrifugal separators with rotating seals,which have not been considered closed and sterile by the FDA. Thus, inthose situations the deglycerized red cells have a maximum storage ofonly twenty-four hours, a major disadvantage.

Thawed blood processing system 2B includes broadly two major steps. Thefirst step is the predilution step where saline is added to the thawedblood. The second step is the wash process in which a recirculation loopis used to wash free plasma hemoglobin and other waste material from thethawed blood.

As in the earlier embodiments of FIGS. 2A and 12, the termination oflines extending out from the cassette are indicated by dashed lines inFIG. 13. System 2B includes a recirculation loop 240 having a number ofblood processing components along the loop. Specifically, loop 240 has ablood pump 242 which pumps blood along loop through a blood filter 244,through a pressure drop tube 246, through a hollow fiber separator 248,past a pinch valve 250, and into an inlet 252 of a blood recirculationbag 254. Bag 254 is housed within and mechanically manipulated bymechanical bag manipulator 10. Blood recirculation bag 254 has an outlet256 fluidly coupled to blood pump 242 through an ultrasonic sensor 258.Sensor 258 is used to determine when fluid is flowing past the sensoralong line 240. As with the embodiment of FIG. 12, the hematocrit of thefluid entering hollow fiber separator 248 is determined with referenceto the pressure drop taken on either side of the pressure drop tube 246.

Hollow fiber separator 248 has a waste outlet 260 by which waste,typically a saline solution containing free plasma hemoglobin andglycerol, is removed from the fluid passing through the separator bypumping by a waste pump 262 into a waste bag 264 through a waste line266. A blood outlet line 270 is connected to recirculation loop 240 at aT coupling 272 between hollow fiber separator 248 and pinch valve 250.Line 270 continues out past the cassette and is coupled to a bloodoutlet bag 274.

A red cell storage solution bag 276, a 12% saline bag 278, a 0.9%saline/0.2% glucose bag 280 and a thawed blood bag 282, are allsupported by bag hanger assembly 8. The various lines coupled to bags276, 278 and 280 all join together and flow into a saline pump line 286at connection 287. A bacterial filter 284 is positioned along salinepump line 286 upstream of a saline pump 288. Saline pump 288 pumps fluidalong saline pump line 286, past a pinch valve 290 and to a T coupling292 along recirculation loop 240.

The cassette also includes a saline line 294 connected at either end topositions 296, 298 along lines 286, 240. A pinch valve 300 and a checkvalve 302 are used along purge line 294 to permit saline to be initiallypumped through recirculation loop 240 from position 298, through bloodfilter 244, pressure drop tube 246, hollow fiber separator 248 and intoblood recirculation bag 254 when system 2B is first started. Thiseliminates air within the lines to improve system performance and helpprevent damage to the red blood cells passing through the line. Pinchvalves 304, 306, 308 and 310 control the flow of fluid from bags 276,278, 280 and 282.

Initially system 2B has all of its pinch valves closed except for pinchvalves 310, 290, and 250. This permits thawed blood from thawed bloodbag to be pumped by saline pump 288 from thawed blood bag 282 throughsaline pump line 286, into recirculation loop 240 and into bloodrecirculation bag 254. An ultrasonic sensor 312, positioned along a line313 connecting thawed blood bag 282 to line 286, is used to sense whenthawed blood bag 282 is empty. When this occurs, saline pump 288 isautomatically stopped by the controller. Next, pinch valve 310 closesand pinch valve 306 opens to permit a predetermined amount, such as 50ml., of 12% saline from bag 278 to be pumped through line 286 into bloodrecirculation bag 254 while the bag is being manipulated or shaken bymanipulator 10 to ensure that the saline and thawed blood are thoroughlymixed. Contact of the thawed blood with the saline helps to shrink thered blood cells and force the glycerin out of the red blood cells. Anequilibration time of about 3 minutes follows pumping of the 12% salineinto bag 254; during this time saline pump 288 is off but bagmanipulator 10 continues to manipulate bag 254. Saline pump 288 isoperated to permit saline from bag 267 to pass into recirculation loop240 to help remove most of the air from the recirculation loop. Pinchvalves 306, 300, and 250 are open during air removal. Pinch valve 306 isclosed and pinch valve 308 is opened so that saline pump 288 can beactuated to pump the saline/glucose mixture in bag 280 into bag 254. Afixed volume, such as 250 ml, of saline/glucose is pumped into bag 254at a fixed flow rate while bag 254 is being manipulated by manipulator10. Pinch valve 308 is then closed and saline pump 288 stops operatingfor a second equilibration period while manipulator 10 continues tomanipulate or shake bag 254.

After this initial mixing process, the wash process of the thawed blood,saline and glucose mixture in bag 254 is begun. During the wash processpinch valve 308, 290 and 250 are opened while the other pinch valves areclosed. The initial wash process occurs through the action saline pump288 pumping the saline/glucose mixture into loop 240 and blood pump 242pumping the fluid mixture in bag 254 through recirculation loop 240 sothat waste, primarily free plasma hemoglobin, glycerol and a salinesolution, is removed from the loop by hollow fiber separator 248 andpumped into waste bag 264 by waste pump 262. When the blood isconsidered washed, such as after a predetermined period of time, salinepump 288 is stopped, pinch valve 308 is closed and blood pump 242 andwaste pump 262 continue to operate. This process is complete when atotal volume of perhaps 800 ml of saline has been consumed. Then pinchvalve 250 is closed, pinch valve 314 is opened and waste pump 262 isstopped which permits pump 242 to pump the washed blood at the desiredhematocrit into blood outlet bag 274. A purging of red cells fromseparator 248 takes place by operating saline pump 288 to pump a volumeof saline into recirculation bag 254 and then operating blood pump 242to pump this saline through the separator, pushing residual red cellsahead of it into bag 274. Bag 274 can be separated from system 2B bypinching, sealing and cutting the tubing attached to the blood outletbag.

During the washing step it is desirable to maintain a fixed pressure atthe inlet of separator 248 by varying the operating speeds and flows ofthe waste pump and saline pump. This causes the saline flow rate to belower and the waste flow rate to be higher when the hematocrit is lower.Doing so maintains the separator inlet hematocrit at an essentiallyfixed value and achieves consistent system and process performance.

The systems of FIGS. 14–17, described below, illustrate variousstructure for attaching the various bags to the cassettes. Some bagscome pre-attached to the cassette, such as bags 12, 404, 404A of FIG.17. This is indicated in FIGS. 14–17 by a plain, direct connection tothe cassette. Break valves are used when fluid-filled bags arepre-attached to the cassette; this keeps the contents in the bags untiloperation of the system is to begin. Two common ways to make non-sterileconnections to fluid-containing bags are through the use of spikes andLuer connectors; bacterial filters for the fluids are preferably used inthese situations.

FIG. 14 is directed to an alternative embodiment of the thawedprocessing system 2B of FIG. 13 with like components referred to by likereference numerals. The primary differences between system 2B of FIG. 13and system 2C of FIG. 14 are as follows. A thawed blood pump 320 is usedalong a line 322 extending from the thawed blood (glycerolized red bloodcell) bag 282 to line 286 just downstream of solenoid pinch valve 290.Also, waste pump 262 has been eliminated from along line 266. It hasbeen found that the separator 248 inlet pressure is sufficient to allowthe waste to collect in waste bag 264 to eliminate the need for wastepump 262. The blood pump 242 flow rate is controlled to achieve anoptimal value of separator inlet pressure PT1 to obtain high blood flowrates and low levels of free plasma hemoglobin or low levels ofhemolysis. The free plasma hemoglobin (FPH) sensor 324, positionedbetween pinch valve 325 and waste bag 264, is used to measure the levelof FPH in the waste line, to monitor this value in a digital display, towarn when it is too high at the end of the process, or to terminate thewash process when a satisfactory low level of FPH has been reached.

Pressure drop tube 246, pressure isolator P2 and pressure isolator P4 ina FIG. 13 embodiment has been eliminated and replaced by a hematocritsensor 326 which senses the hematocrit by optical means by using lighttransmission or light scattering at specific wavelengths. Pressureisolator PT1 of FIG. 14, which corresponds to pressure isolator P1 ofFIG. 13, is used to measure separator inlet pressure in order to controlblood pump 242 flow rate at optimal values according to a controlalgorithm and may be used in conjunction with or in replacement of thehematocrit sensor 326 for this purpose. A static mixer 328 is used alongline 286 between the intersection 329 of lines 322 and 286 andintersection 292. Static mixer 328 is used to help ensure the propermixing of the thawed blood from bag 282 with the 12% saline solutionfrom bag 278. A sterile dock 330 positioned along line 322 betweenultrasonic sensor 312 and bag 282 is used to perform a sterileattachment of the thawed blood bag 282 to the sterile disposable setduring the setup of the disposable set. An ultrasonic sensor 332 ispositioned just upstream from pump 288 and is used to provide anindication to the controller when bubbles appear in the line asindicating the source of the particular solution being pumped has beeneffectively exhausted. The operation of system 2C is substantially thesame as the operation of system 2B of FIG. 13 with the slightmodifications discussed above.

The process carried out by FIG. 14 is essentially identical to that ofFIG. 13. Early in the process there is a priming step that adds 0.9%saline solution from the bag 280 to the hollow fiber separator 248 andthe blood filter 244 to remove air and replace it with saline; most ofthat saline ends up in the waste bag and replacing air in both devices.The 12% saline solution from bag 278 is added by using the solutionspump 288; it flows through static mixer 328 simultaneously with thethawed glycerolized RBCs pumped out of bag 282 by thawed blood pump 320so the flow streams of the 12% saline and the RBCs mix in junction 329and also in static mixer 328 before they flow into recirculation bag254. That process is complete when all of the thawed glycerolized RBCsare removed from bag 282. Recirculation bag 254 is shaken during theaddition of 12% saline. Then there is about a three minute equilibrationtime when bag 254 is shaken but nothing else is happening. Then acertain quantity of the 0.9% saline 0.2% glucose solution from bag 280is added by the solutions pump 288 through the static mixer 328 and intothe recirculation bag 254 where it mixes in the bag with the blood. Atthat point the recirculation process begins. The blood pump 242 beginsto pump blood through the hollow fiber separator and back into therecirculation bag 254 which is shaken to accomplish mixing and maintaina homogeneous mix in the recirculation bag. The wash process that occursis the concentration of blood to a higher hematocrit through the hollowfiber separator so that the hematocrit level for blood exiting theseparator is raised. Then saline is added at point 272 using thesolutions pump 288 to pump the 0.9% saline 0.2% glucose to point 272,the objective being to replace waste that has been removed by the hollowfiber separator 248 with an equivalent flow of saline, thus keeping thehematocrit in the recirculation bag 254 constant. This wash process isthe same as that performed in FIG. 13 and proceeds for several minutes,during which time about 1500 ml saline are consumed and a similar amountof waste is produced. At that point the washing is complete; glycerolhas been removed from the blood as has FPH. (System 2C could also beused to remove other compounds, such as viral inactivation compounds,from blood.) The blood pump 248 is used to pump blood out of therecirculation bag 254 into the deglycerolized RBC bag 274. Solutionsfrom one or both of bags 276, 280 are added using the solutions pump 288to the recirculation bag 254 purging red cells from separator 248 andthen that is pumped out of the recirculation bag with blood pump 242into the deglycerolized RBC bag 274 to add a storage solution to redcells that have been previously concentrated by the wash process up to afairly high hematocrit.

FIG. 15 illustrates a blood glycerolization processing system 2D inwhich concentrated red blood cells are stabilized by the addition ofglycerol for subsequent freezing and long term storage. System 2includes a container 334 containing, in this embodiment, a 57% glycerolsolution, a red blood cell bag 336 containing concentrated red bloodcells, preferably at a hematocrit of about 60 to 80%. Red blood cell bag336 is connected to a line 338 of the cassette by a sterile dock 340while container 334 is connected to line 342 using a conventional spike344. Container 334 is typically not collapsible so that a conventionalvent needle 346 is used to prevent a vacuum being created withincontainer 334 as the contents are removed by glycerol pump 348 situatedalong line 342. A recirculation bag 350 is connected along arecirculation loop 352 of the cassette and is agitated by bag shaker354. A recirculation pump 356 is situated along loop 352 downstream fromthe outlet 357 of bag 350. Loop 352 intersects with line 338 at ajunction 358 positioned just downstream from a blood pump 360 along line338. A glycerolized RBC collection bag 362, which is used to hold theglycerolized red blood cells, is connected to line 364 of the cassette,line 364 connecting to recirculation loop 352 at a junction 366. Ahollow fiber separator 368 is positioned along loop 352 betweenjunctions 358 and 366. Hollow fiber separator 368 includes a first inlet370 downstream of junction 358 and a second inlet 372 coupled to thedistal end of line 342 so that hollow fiber separator 368 is suppliedboth glycerol from container 334 and red blood cells from bag 336. Thepressures at inlets 370, 372 are monitored by pressure isolators 371,373. Hollow fiber separator 368 also includes a waste exit 374 connectedto a waste line 376. Waste line 376 has a pinch valve 377 between exit374 and a waste bag 378. The hematocrit of the flow exiting the mainexit 380 of hollow fiber separator 368 is sensed by a hematocrit sensor382 for control purposes. Also, ultrasonic air sensors 384, 386 arepositioned along line 338 and loop 352 to sense when air is being pumpedalong those lines indicating that bag 336 or bag 350 is or may be empty.Solenoid pinch valve 388, 390 are used along loop 352 between entrance392 to bag 350 and junction 366 and along line 364 between bag 362 andjunction 366.

The glycerolization process of system 2D of FIG. 15 begins by pumpingthe blood, specifically concentrated red cells (at about a 60–80%hematocrit) which contains some plasma and possibly anticoagulant, alongline 338, through first inlet 370 and through the interiors of theporous hollow fibers housed within the interior of separator 368.Simultaneously with this pumping of blood through separator 368,glycerol solution is being pumped from container 334 by pump 348 alongline 342, through second inlet 372 and into that portion of the interiorof separator surrounding the hollow fibers; pinch valves 377, 390 areclosed and pinch valve 388 is opened when pumps 348, 360 are operating.This causes glycerol to be forced through the porous walls of the hollowfibers and into the blood flowing through the hollow fibers. In this wayglycerol is quickly added to and mixed with the blood, which isimportant to prevent hemolysis. Separator 368 is thus initially used asa mixing device for mixing glycerol with blood. The glycerol is meteredinto the blood by controlling the flow rates of blood and glycerol toget a desired concentration of glycerol and red blood cells. This bloodand glycerol mixture in separator 368 passes through main exit 380,along loop 352 and into recirculation bag 350.

Once all blood has been recovered from bag 336, the blood and glycerolmixture is collected in bag 350, pumps 348, 360 are stopped, pinch valve377 is opened and recirculation pump 356 is operated to pump the bloodand glycerol mixture through separator 368 while measuring thehematocrit at hematocrit sensor 382. Excess glycerol, plasma and otherliquid mixed with the red cells passes from the inside to the outside ofthe porous walls of the hollow fibers, passes through waste exit 374,along waste line 376 and into waste bag 378. This recirculation throughloop 352 continues until the desired hematocrit, sensed by sensor 382,is reached. The concentrated red cells and glycerol may be left inrecirculation bag 350 or may be pumped into bag 362, whichever bag isused specifically to freeze and store the glycerolized red cells.

One of the purposes for initially adding excess amounts of glycerol isto aid removing most of the plasma and other liquid which is found inthe blood in bag 336. The glycerolizing process also forces liquid outof the red cells replacing most or some of this liquid within the cellsby glycerolizing liquid; this is desirable for effective frozen storageof the red cells. Removal of this liquid is also aided by adding andthen removing excess glycerol.

FIG. 16 illustrates an alternative embodiment of the automatic wholeblood collection system 2 of FIG. 2A with like elements referred to withlike reference numerals. System 2E differs from system 2 in severalways. Whole blood filter 70 has been moved out of recirculation loop 68so that it is now between junction 66 and blood pump 46A. Line 94 nolonger connects to line 44 at junction 98; rather, line 94 connects to aline 396 at a junction 398. Line 396 also connects to lines 52 and 68 atjunctions 400 and 402, respectively. In addition, an RBC administrationbag 404 is used to receive the concentrated red cells after storagesolution from bag 92 has been added by pumping the mixture out ofrecirculation bag 12 and into bag 404. Bag 404 is connected to a line406 on the cassette which connects to loop 68 at a junction 408. Air inthe lines is sensed by three different ultrasonic air detectors 410,412, 414 positioned along lines 44, 52 and 68, respectively. Additionalpinch valves 416, 418 and 419 are used along recirculation loop 68 andlines 396 and 406, respectively. A hematocrit sensor 420 is used alongrecirculation loop 68 just upstream of plasma separator 74. Anelectronic scale 422 is used to monitor the weight of plasma bag 78 soto provide the controller with appropriate information as to the weightof the contents of the bag. Break valves 424, 426 are used to couplebags 50 and 92 to lines 52 and 94. Bags 12, 404 and 78 are, in thisembodiment, preattached to the cassette during manufacture.

The use of whole blood filter 70 is not necessary when red blood celladministration bag 404 is replaced by a separation bag that is used inan automated blood component separation system sold by Mission Medical,Inc. of Fremont, Calif. as Mission 3000 disposable set. This centrifugalautomated blood component separation system will serve the function of awhole blood filter by removing leukocytes from red blood cells. Anexample of such a centrifuged separation bag is described in U.S. PatentApplication No. 60/143,036, filed Jul. 9, 1999.

FIG. 17 illustrates an alternative embodiment of the automatic bloodcollection system 2E of FIG. 16 with like reference numerals referringto like elements. Bags 50 and 92 are connected to lines 52 and 92 byspikes 428, 430 rather than being preattached to the cassette. Whenanticoagulant bag 50 is not preattached, a bacterial filter 432 is usedpreferably along line 52 to prevent the introduction of bacteria intothe system. A line 434 is used to couple a junction 436 along line 52with the terminal end 438 of line 94. A line 440 couples terminal end438 of line 94 with a junction 441 along line 76. A second RBCadministration bag 404A is used and is connected to line 406 by a line442. A line 444 couples junction 408 along recirculation loop 68 and ajunction 446 along line 52. A blood filter 448 is positioned along aline 450 connecting lines 444 and 44. Blood filter 448 is used when redcells are being returned to the donor, that is during the collection ofplasma as is discussed in more detail below. A saline bag 452, which asindicated in FIG. 17 is not a part of the cassette, it is coupled toline 440 via a line 454. In addition to the above described elements,six solenoid pinch valves are used with system 4F. In particular, pinchvalve 456 is used between junction 436 and spike 428 along line 52,pinch valve 458 is used between junction 446 and ultrasonic air detector412, pinch valve 460 is used along line 444, pinch valve 462 is usedalong line 450, pinch valve 464 is used along line 454 and pinch 466 isused along line 440 between junction 442 and line 454.

System 2F permits the collection of two units of whole blood. After thefirst unit of whole blood has been collected and separated, the plasmafrom the first unit is returned to the donor along with saline so thatthe donor suffers no change in total liquid volume within theircirculatory system. This is repeated for the second unit of blood.System 2F is used as follows.

The collection of each unit of whole blood is done in the same fashionas described in FIGS. 2A and 16. A number of components have been addedso that after one unit has been collected and separated in therecirculation bag 12, the red cells are pumped into an administrationbag 404, 404A and storage solution from bag 92 is used to obtainlong-term (about 35–42 days) refrigerated red cell storage. First,storage solution from bag 92 is added through the plasma separator 74and into the recirculation bag 12 partly to purge the separator andpartly simply to add the red cell storage solution to bag 12. The bloodis then pumped out of the recirculation bag 12 into one of the RBCadministration bags 404, 404A. It is also feasible to use theanticoagulant from bag 50 instead of the red cell storage solution frombag 92. Either the red cell storage solution or the anticoagulant arepumped by the anticoagulant pump 54A through the bacterial filter 432,through valve 460, through plasma separator 74 and then into therecirculation bag 12. Either one of the anticoagulant or the storagesolution can perform the purging function so the red cell storagesolution may be used only when long-term storage is desired.

The next step is to pump the plasma out of the plasma bag 78 back intothe donor. To do that anticoagulant pump 54A is used with valve 466 openand valves 80A and 464 closed. Plasma is pumped out of the plasma bag78, through the bacterial filter 432, through open valve 458 and backinto the donor through needle 40. In this case the blood pump 46A is offand acts as a valve so that the flow goes into the donor and not backinto the system. Ultrasonic sensor 412 is used to detect when the plasmabag 78 is empty, which is when air bubbles arrive in sensor 412, so flowis terminated when blood plasma bag 78 is empty. Then valve 466 closes,valve 464 opens, and saline is pumped through the same route, that isthe anticoagulant pump 54A through the bacterial filter 432 and throughopen valve 458 back to the donor until the plasma plus the salinereturned to the donor add up to the amount of whole blood removed fromthe donor.

In the event plasma is to be retained and not given back to the donor,it may be necessary to give red cells back to the donor. That can beaccomplished by pumping blood out of the recirculation bag 12 or a redcell administration bag 404, 404A using either the recirculation pump72A and the blood pump 46A pumping through the blood infusion filter 448and open valve 462 back to the donor through needle 40. If the blood hasbeen put into one of the RBC administration bags 404, 404A, then it ispumped through the blood filter 70 and open valve 462 by the blood pump46A. Blood infusion filter 448 is only used when pumping red cells backinto the donor. Filter 448 is a particulate filter with a pore size of20–80 microns intended to remove particulates from red cells that aregiven back to the donor.

FIGS. 18–20 illustrate an automated blood system 2G made according tothe invention. Note the system 2G can be used for any of theabove-discussed blood processing methods through the appropriate choiceof programs and the use of the appropriate cassette and bags. System 2Gwill be discussed very briefly pointing out certain similarities anddifferences with system 2 as shown in FIG. 1 with like referencenumerals referring to like elements. Housing 4A includes a user controlpanel 16A mounted to a sloped portion of the top 6A of the housing asopposed to its front panel 14A as in the FIG. 1 embodiment. Door 34Acovers the entire front panel 14A when in the closed position of FIG. 18and is maintained in the closed position by being latched with handle160A. FIG. 19 illustrates system 2G but with the cassette, bags andassociated tubing removed for clarity of illustration. Instead of beingslideably mounted to a cassette 24 as shown in FIG. 2, the cassette ishung against front panel 14A by a pair of outwardly extending pins 470.Also, instead of using a bag manipulator 10 above housing 4 as in FIG.1, the contents of recirculation bag 12, also called storage bag 12, areagitated by the movement of a bag shaker 10A extending from front panel14A with bag 12 being captured between bag shaker 10A and a bag shakersupport surface 472, shown in FIG. 20.

As used herein, blood typically includes whole blood, concentrated redblood cells, glycerolized blood and other blood products including asubstantial portion of red blood cells.

Modification and variation can be made to the described embodimentswithout departing from the subject of the invention as defined by thefollowing claims. For example, the door or the cassette assembly, orboth, could be designed to be completely removable from the housingrather than being pivotally mounted to the housing. The roller tracks orthe pinch surfaces, or both, could be formed as a part of the cassetteassembly instead of the door. Ultrasonic, as well as otherremote-sensing flow detectors, may be used to detect fluid flows alongthe various pathways. In the autotransfusion system 2A of FIG. 12, thehematocrit can be measured using a hematocrit sensor just downstream ofblood pump 174 instead of the use of laminar flow tube 176, togetherwith pressure access ports 178, 180.

Any and all patents, applications and printed publications referred toabove are incorporated by reference.

1. A blood washing system comprising: an endless recirculation loop,fluidly coupled to an inlet for a source of blood; a blood separator,having an entrance port, an exit port and a removed fraction port,defining a portion of the recirculation loop between the entrance andexit ports; a pump situated along the recirculation loop operable topump blood from and through the recirculation loop; the blood separatorconfigured to separate blood entering the entrance port into a retainedfraction, which passes through the exit port, and a removed fraction,which passes through the removed fraction port, at least a portion ofthe retained fraction passing through the blood separator at least asecond time; a replacement fluid source fluidly coupled to therecirculation loop, whereby the replacement fluid source is configuredto replace at least a part of the removed fraction; and control meansprogrammed to control the addition of replacement fluid so as toregulate hematocrit of the fluid in the recirculation loop, wherein thehematocrit is determined by measuring resistance to flow within theblood separator.
 2. The system according to claim 1 wherein the controlmeans acts to maintain said hematocrit within a desired range.
 3. Thesystem according to claim 1 wherein the removed fraction comprises atleast one of plasma, free plasma hemoglobin, leukocytes, and viralinactivation compounds.
 4. The system according to claim 1 wherein theretained fraction comprises red blood cells.
 5. The system according toclaim 1 wherein the retained fraction comprises plasma.
 6. The systemaccording to claim 1 wherein the replacement fluid is saline.
 7. Thesystem according to claim 1 wherein the replacement fluid includesglucose.
 8. The system according to claim 1 wherein the pump stops whenthe amount of blood taken from the source has reached a predeterminedamount and then the blood separator stops when the hematocrit hasreached a predetermined hematocrit.
 9. The system according to claim 1wherein the source of blood is a chosen one of a donor vein, a patient'ssurgery site, a container of concentrated red blood cells and acontainer of thawed blood.
 10. A method for washing blood comprising:accessing a source of blood; pumping blood from the source of bloodthrough a recirculation loop, the recirculation loop comprising a bloodseparator; separating the blood passing through the blood separator intoa removed fraction and a retained fraction; removing the removedfraction from the recirculation loop; said pumping step being carriedout so that at least a portion of the retained fraction passes throughthe blood separator at least a second time; adding a replacement fluidto the recirculation loop; determining a desired hematocrit of the bloodin the recirculation loop by measuring resistance to flow within theblood separator; and the adding step comprising controlling the amountof the replacement fluid added according to the desired hematocrit ofthe blood in the recirculation loop.
 11. The method according to claim10 wherein the removed fraction comprises at least one of plasma, freeplasma hemoglobin, leukocytes, and viral inactivation compounds.
 12. Themethod according to claim 10 wherein the retained fraction comprises redblood cells.
 13. The system according to claim 10 wherein the retainedfraction comprises plasma.
 14. The method according to claim 10 whereinthe replacement fluid is saline.
 15. The method according to claim 10wherein the replacement fluid includes glucose.
 16. The method accordingto claim 10 wherein the blood pumping step is stopped when the amount ofblood taken from the source has reached a predetermined amount and thenthe blood separating step is stopped when the desired hematocrit hasreached a predetermined hematocrit.
 17. The method according to claim 10wherein the accessing step is carried out by fluidly coupling therecirculation loop with an inlet for a source of blood, the source ofblood being a chosen one of a donor vein, a patient's surgery site, acontainer of concentrated red blood cells and a container of thawedblood.
 18. The system according to claim 10 wherein the desiredhematocrit is at least about 45%.
 19. The system according to claim 10where in the desired hematocrit is about 60–80%.